OBJECTIVES: Portfolio management is commonly used to prioritize investments within the private sector, but is not used widely to manage public research investments due to the difficulty of defining and quantifying appropriate measures of risk and return.  We recently developed a novel tools to estimate the risk and return of publicly funded cancer clinical trials.  Our objective was to use these metrics and apply a proof of concept portfolio management approach within SWOG, a large cancer clinical trials cooperative group.  METHODS: The sample portfolio included 9 randomized Phase II/III clinical trial concepts reviewed by SWOG between 2008-2013, of which 5 were approved and 4 were not.  Risk was defined as the probability of insufficient accrual (<50% of target) and measured using a previously validated prediction model.  Value of Information methods were used to estimate societal return, defined both as the population-level expected health benefits (clinical return) or clinical and economic benefits (net return) of acquiring additional information to inform a decision and measured. We compared the risk-adjusted expected returns of the observed portfolio of approved trials to hypothetical alternative portfolios in which different trials might have been funded.   RESULTS: The clinical return of SWOG’s sample portfolio was valued at $11.3 billion.  A hypothetical alternative portfolio of trials requiring 200 fewer patients than the observed portfolio was expected to have a clinical return of $26.3 billion. The net return of SWOG’s observed sample portfolio was $2.7 billion.  An alternative hypothetical portfolio that includes four trials and requires 400 fewer patients than the observed portfolio was expected to have a net return of approximately $9.6 billion.  CONCLUSIONS: A portfolio management approach appears to be a feasible and potentially useful response to the Institute of Medicine’s call for more systematic approaches to prioritize trials concepts within the cancer clinical trials cooperative groups.